A Phase II Uncontrolled Study of BAY73-4506 in Previously Untreated Patients With Metastatic or Unresectable RCC
Study Details
Study Description
Brief Summary
This is a uncontrolled, open-label, non-randomized Phase II study of oral BAY73-4506 to evaluate the response rate of BAY73-4506 in previously untreated patients with metastatic or unresectable renal cell cancer (RCC).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The final analysis of efficacy will be performed after last patient has been treated for at least 6 months. Additional periodic safety and efficacy data reviews will be performed for any patients continuing to receive study drug afterwards.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regorafenib (Stivarga, BAY73-4506) Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
Drug: Regorafenib (Stivarga, BAY73-4506)
Patients will be treated with BAY73-4506 160 mg po qd for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off). Patients will continue treatment with BAY73-4506 until disease progression, intolerable toxicity, or patient refusal to continue with the study or investigator decision to remove the patient from study.
|
Outcome Measures
Primary Outcome Measures
- Objective Tumor Response [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee.
- Tumor Response [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.
Secondary Outcome Measures
- Disease Control [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.
- Overall Survival [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009).]
Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
- Progression-free Survival (PFS) [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.
- Time to Progression (TTP) [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.
- Duration of Response [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.
- Duration of Stable Disease (SD) [From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks]
Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.
Other Outcome Measures
- Objective Tumor Response (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the RECIST committee.
- Tumor Response (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee.
- Disease Control (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating.
- Overall Survival (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011).]
Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
- Progression-free Survival (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation.
- Time to Progression (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation.
- Duration of Response (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment.
- Duration of Stable Disease (Update) [From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks]
Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female patients >/= 18 years of age.
-
Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (renal cell carcinoma histologically) or cytologically documented.
-
Patients must be previously untreated for advanced disease. Prior palliative radiation therapy is allowed if the target lesion(s) are not included within the radiation field and no more than 30% of the bone marrow is irradiated.
-
Patients who have at least one uni-dimensional measurable lesion by computed tomography (CT-scan) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST).
-
Patients with "Intermediate" or "Low" risk per the Motzer score.
-
Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1.
-
Adequate bone marrow, renal and hepatic function as assessed by the following laboratory requirements to be conducted within 7 days prior to study drug treatment
Exclusion Criteria:
-
Patients who have received prior systemic treatment regimens for RCC.
-
Uncontrolled/unstable cardiac disease
-
Uncontrolled hypertension
-
Active clinically serious infections (> Common Terminology Criteria for Adverse Events [CTCAE] grade 2 )
-
History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
-
Known history or symptomatic metastatic brain or meningeal tumours
-
Patients with seizure disorder requiring medication
-
Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event >/= CTCAE Grade 3 within 4 weeks of first dose of study.
-
Pregnant or breast-feeding patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Los Angeles | California | United States | 90033 | |
| 2 | Houston | Texas | United States | 77030 | |
| 3 | Helsinki | Finland | 00290 | ||
| 4 | Turku | Finland | FIN-20521 | ||
| 5 | Nantes | France | 44020 | ||
| 6 | Paris | France | 75014 | ||
| 7 | Frankfurt | Hessen | Germany | 60596 | |
| 8 | Dresden | Sachsen | Germany | 01307 | |
| 9 | Berlin | Germany | 10967 | ||
| 10 | Hamburg | Germany | 20246 | ||
| 11 | Bialystok | Poland | 15-027 | ||
| 12 | Lublin | Poland | 20-090 | ||
| 13 | Poznan | Poland | 60-569 | ||
| 14 | Leicester | Leicestershire | United Kingdom | LE1 5WW | |
| 15 | Bristol | United Kingdom | BS2 8ED | ||
| 16 | Cambridge | United Kingdom | CB2 0QQ | ||
| 17 | London | United Kingdom | SE1 9RT | ||
| 18 | Northwood | United Kingdom | HA6 2RN |
Sponsors and Collaborators
- Bayer
Investigators
- Study Director: Bayer Study Director, Bayer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- Click here to find results for studies related to Bayer Healthcare products.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.
Publications
None provided.- 11726
- 2008-000107-28
Study Results
Participant Flow
| Recruitment Details | Male or female untreated participants, who were at least 18 years of age, with metastatic and/or unresectable, measurable predominantly clear cell renal cell cancer (RCC) histologically or cytologically documented could participate in this study at 18 centers in 6 countries. |
|---|---|
| Pre-assignment Detail | Of 64 enrolled participants, 49 received study medication, and 15 were screen failures due to protocol violation (12 participants), withdrawal of consent (1 participant), adverse event (2 participants). |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Period Title: Overall Study | |
| STARTED | 49 |
| COMPLETED | 1 |
| NOT COMPLETED | 48 |
Baseline Characteristics
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Overall Participants | 49 |
| Age (Years) [Median (Full Range) ] | |
| Median (Full Range) [Years] |
62.0
|
| Sex: Female, Male (Count of Participants) | |
| Female |
22
44.9%
|
| Male |
27
55.1%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants) | |
| 0 |
30
61.2%
|
| 1 |
19
38.8%
|
| Overall Motzer Score (Count of Participants) | |
| Low |
24
49%
|
| Intermediate |
25
51%
|
Outcome Measures
| Title | Objective Tumor Response |
|---|---|
| Description | Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) committee. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Number [Percentage of participants] |
31.3
63.9%
|
| Title | Tumor Response |
|---|---|
| Description | Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Complete Response (CR) |
0.0
0%
|
| Partial Response (PR) |
31.3
63.9%
|
| Stable Disease (SD) |
50.0
102%
|
| Progressive Disease (PD) |
10.4
21.2%
|
| Not Assessable |
8.3
16.9%
|
| Title | Disease Control |
|---|---|
| Description | Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Number [Percentage of participants] |
62.5
127.6%
|
| Title | Overall Survival |
|---|---|
| Description | Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
NA
|
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
251
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
251
|
| Title | Duration of Response |
|---|---|
| Description | Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects from ITT population with a response of CR or PR were included in this evaluation. |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 15 |
| Median (95% Confidence Interval) [Days] |
NA
|
| Title | Duration of Stable Disease (SD) |
|---|---|
| Description | Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 13 months later (13May2008 - 31May2009). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects from ITT population who achieved objective response of CR or PR were excluded from this evaluation. |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 29 |
| Median (95% Confidence Interval) [Days] |
172
|
| Title | Objective Tumor Response (Update) |
|---|---|
| Description | Objective tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears] or Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline]) observed during trial period assessed according to the RECIST committee. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Number [Percentage of participants] |
39.6
80.8%
|
| Title | Tumor Response (Update) |
|---|---|
| Description | Tumor response of a participant was defined as the best tumor response (confirmed Complete Response [CR, tumor disappears], Partial Response [PR, sum of lesion sizes decreased at least 30% from baseline], Stable Disease [SD, steady state of disease], or Progressive Disease [PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions]) observed during trial period assessed according to the RECIST committee. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Complete Response (CR) |
0.0
0%
|
| Partial Response (PR) |
39.6
80.8%
|
| Stable Disease (SD) |
41.7
85.1%
|
| Progressive Disease (PD) |
10.4
21.2%
|
| Not Assessable |
8.3
16.9%
|
| Title | Disease Control (Update) |
|---|---|
| Description | Disease control was defined as the percentage of participants who had a best response rating of CR (tumor disappears), PR (sum of lesion sizes decreased at least 30% from baseline), or SD (steady state of disease) that was maintained for at least 28 days from the first demonstration of that rating. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Evaluable for response (Primary analysis population) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 48 |
| Number [Percentage of participants] |
62.5
127.6%
|
| Title | Overall Survival (Update) |
|---|---|
| Description | Overall survival (OS) was calculated as the time from the first date of receiving study medication to death, due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
NA
|
| Title | Progression-free Survival (Update) |
|---|---|
| Description | PFS was calculated as time from first date of receiving study drug until date of first observed disease progression (PD) (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before PD was documented. The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD or death at time of analysis were censored at last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
335
|
| Title | Time to Progression (Update) |
|---|---|
| Description | TTP was calculated as time from first date of receiving study drug until date of first documented disease progression (PD) (radiological or clinical, whichever was earlier). The actual date of tumor assessments (i.e., date on which radiological procedure was performed, rather than the scheduled date) was used for this calculation to determine both the event date and censoring date. Patients without PD at time of analysis were censored at last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| intention-to-treat (ITT) |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [Days] |
335
|
| Title | Duration of Response (Update) |
|---|---|
| Description | Duration of response was defined as the time from the first documented objective response of PR or CR, whichever was earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects from ITT population with a response of CR or PR were included in this evaluation. |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 19 |
| Median (95% Confidence Interval) [Days] |
428
|
| Title | Duration of Stable Disease (Update) |
|---|---|
| Description | Duration of SD was calculated as the time from the first date of receiving study drug until the date of documented PD or the last observation if the subject did not progress. Subjects without disease progression at the time of analysis were censored at the last date of tumor evaluation. |
| Time Frame | From start of treatment of the first participant until database cut-off approximately 37 months later (13May2008 - 1Jun2011). Assessed every 8 weeks for 6 months, then every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects from ITT population who achieved objective response of CR or PR were excluded from this evaluation. |
| Arm/Group Title | Regorafenib (Stivarga, BAY73-4506) |
|---|---|
| Arm/Group Description | Participants received Regorafenib 160 mg per os (po) every day (qd) for 3 weeks on 1 week off of every 4 week cycle |
| Measure Participants | 25 |
| Median (95% Confidence Interval) [Days] |
119
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | Acronyms used in Adverse events section: Gastrointestinal (GI), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Common Terminology Criteria for Adverse Events (CTCAE). | |
| Arm/Group Title | Regorafenib (BAY73-4506) | |
| Arm/Group Description | Subjects received regorafenib 160 mg po qd for 3 weeks of every 4 week cycle (3 weeks on, 1 week off). | |
All Cause Mortality |
||
| Regorafenib (BAY73-4506) | ||
| Affected / at Risk (%) | # Events | |
| Total | 39/49 (79.6%) | |
Serious Adverse Events |
||
| Regorafenib (BAY73-4506) | ||
| Affected / at Risk (%) | # Events | |
| Total | 32/49 (65.3%) | |
| Cardiac disorders | ||
| Angina unstable | 1/49 (2%) | 2 |
| Atrial fibrillation | 1/49 (2%) | 1 |
| Cardiac arrest | 2/49 (4.1%) | 2 |
| Myocardial infarction | 2/49 (4.1%) | 2 |
| Gastrointestinal disorders | ||
| Abdominal pain | 1/49 (2%) | 1 |
| Diarrhoea | 1/49 (2%) | 1 |
| Gastrointestinal pain | 1/49 (2%) | 1 |
| Haematemesis | 1/49 (2%) | 1 |
| Small intestinal obstruction | 1/49 (2%) | 1 |
| Vomiting | 1/49 (2%) | 1 |
| General disorders | ||
| Chest pain | 2/49 (4.1%) | 2 |
| Fatigue | 1/49 (2%) | 1 |
| Malaise | 1/49 (2%) | 1 |
| Pyrexia | 1/49 (2%) | 1 |
| General physical health deterioration | 2/49 (4.1%) | 2 |
| Hepatobiliary disorders | ||
| Cholecystitis | 1/49 (2%) | 2 |
| Hepatic function abnormal | 1/49 (2%) | 1 |
| Bile duct obstruction | 1/49 (2%) | 1 |
| Infections and infestations | ||
| Cellulitis | 1/49 (2%) | 1 |
| Infection | 1/49 (2%) | 2 |
| Pneumonia | 1/49 (2%) | 1 |
| Sepsis | 1/49 (2%) | 2 |
| Injury, poisoning and procedural complications | ||
| Fracture | 1/49 (2%) | 3 |
| Humerus fracture | 1/49 (2%) | 1 |
| Procedural intestinal perforation | 1/49 (2%) | 2 |
| Investigations | ||
| Haemoglobin decreased | 1/49 (2%) | 2 |
| Metabolism and nutrition disorders | ||
| Hypocalcaemia | 1/49 (2%) | 1 |
| Hypomagnesaemia | 1/49 (2%) | 1 |
| Hypovolaemia | 1/49 (2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 1/49 (2%) | 1 |
| Back pain | 1/49 (2%) | 1 |
| Flank pain | 1/49 (2%) | 2 |
| Muscular weakness | 1/49 (2%) | 1 |
| Musculoskeletal pain | 1/49 (2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Bone neoplasm | 1/49 (2%) | 1 |
| Metastases to spine | 1/49 (2%) | 1 |
| Ovarian adenoma | 1/49 (2%) | 1 |
| Nervous system disorders | ||
| Loss of consciousness | 1/49 (2%) | 1 |
| Sciatica | 1/49 (2%) | 1 |
| Syncope | 2/49 (4.1%) | 3 |
| Renal and urinary disorders | ||
| Renal failure | 4/49 (8.2%) | 7 |
| Acute kidney injury | 1/49 (2%) | 2 |
| Reproductive system and breast disorders | ||
| Ovarian cyst | 1/49 (2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Epistaxis | 1/49 (2%) | 2 |
| Haemoptysis | 1/49 (2%) | 1 |
| Laryngospasm | 1/49 (2%) | 1 |
| Pleural effusion | 2/49 (4.1%) | 2 |
| Pulmonary embolism | 1/49 (2%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Palmar-plantar erythrodysaesthesia syndrome | 1/49 (2%) | 2 |
| Rash | 1/49 (2%) | 1 |
| Rash generalised | 1/49 (2%) | 1 |
| Surgical and medical procedures | ||
| Tumour excision | 1/49 (2%) | 1 |
| Vascular disorders | ||
| Circulatory collapse | 1/49 (2%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Regorafenib (BAY73-4506) | ||
| Affected / at Risk (%) | # Events | |
| Total | 48/49 (98%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 5/49 (10.2%) | 9 |
| Thrombocytopenia | 5/49 (10.2%) | 11 |
| Gastrointestinal disorders | ||
| Abdominal pain | 13/49 (26.5%) | 37 |
| Abdominal pain upper | 8/49 (16.3%) | 28 |
| Constipation | 17/49 (34.7%) | 112 |
| Diarrhoea | 24/49 (49%) | 215 |
| Dyspepsia | 6/49 (12.2%) | 7 |
| Dysphagia | 4/49 (8.2%) | 5 |
| Glossodynia | 3/49 (6.1%) | 4 |
| Nausea | 16/49 (32.7%) | 46 |
| Oral pain | 6/49 (12.2%) | 35 |
| Stomatitis | 15/49 (30.6%) | 108 |
| Vomiting | 13/49 (26.5%) | 29 |
| General disorders | ||
| Chest pain | 7/49 (14.3%) | 19 |
| Chills | 3/49 (6.1%) | 6 |
| Fatigue | 22/49 (44.9%) | 192 |
| Mucosal inflammation | 6/49 (12.2%) | 11 |
| Oedema peripheral | 4/49 (8.2%) | 13 |
| Pain | 6/49 (12.2%) | 31 |
| Pyrexia | 9/49 (18.4%) | 14 |
| Infections and infestations | ||
| Bronchitis | 3/49 (6.1%) | 3 |
| Infection | 3/49 (6.1%) | 3 |
| Nasopharyngitis | 9/49 (18.4%) | 21 |
| Oral candidiasis | 3/49 (6.1%) | 7 |
| Rhinitis | 4/49 (8.2%) | 6 |
| Upper respiratory tract infection | 4/49 (8.2%) | 6 |
| Urinary tract infection | 6/49 (12.2%) | 13 |
| Investigations | ||
| Amylase increased | 4/49 (8.2%) | 12 |
| Blood creatinine increased | 3/49 (6.1%) | 7 |
| Lipase increased | 7/49 (14.3%) | 29 |
| Weight decreased | 8/49 (16.3%) | 86 |
| Metabolism and nutrition disorders | ||
| Hyperuricaemia | 3/49 (6.1%) | 13 |
| Decreased appetite | 16/49 (32.7%) | 104 |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 7/49 (14.3%) | 120 |
| Back pain | 13/49 (26.5%) | 55 |
| Bone pain | 3/49 (6.1%) | 25 |
| Muscle spasms | 6/49 (12.2%) | 53 |
| Musculoskeletal pain | 8/49 (16.3%) | 23 |
| Neck pain | 4/49 (8.2%) | 12 |
| Pain in extremity | 11/49 (22.4%) | 85 |
| Nervous system disorders | ||
| Ageusia | 3/49 (6.1%) | 4 |
| Dizziness | 4/49 (8.2%) | 7 |
| Dysgeusia | 4/49 (8.2%) | 14 |
| Headache | 14/49 (28.6%) | 47 |
| Neuropathy peripheral | 4/49 (8.2%) | 8 |
| Paraesthesia | 4/49 (8.2%) | 61 |
| Psychiatric disorders | ||
| Insomnia | 6/49 (12.2%) | 23 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 6/49 (12.2%) | 15 |
| Dysphonia | 18/49 (36.7%) | 50 |
| Dyspnoea | 16/49 (32.7%) | 48 |
| Epistaxis | 4/49 (8.2%) | 6 |
| Oropharyngeal pain | 3/49 (6.1%) | 7 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 22/49 (44.9%) | 139 |
| Dry skin | 6/49 (12.2%) | 77 |
| Hyperhidrosis | 5/49 (10.2%) | 19 |
| Night sweats | 4/49 (8.2%) | 8 |
| Palmar erythema | 3/49 (6.1%) | 3 |
| Palmar-plantar erythrodysaesthesia syndrome | 34/49 (69.4%) | 402 |
| Pruritus | 5/49 (10.2%) | 16 |
| Rash | 17/49 (34.7%) | 74 |
| Rash generalised | 3/49 (6.1%) | 4 |
| Vascular disorders | ||
| Hypertension | 25/49 (51%) | 338 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The agreed point of publication is 12-18 months after database lock at the earliest. Bayer will have 30-45 days to review publications, and may request an additional publication delay of up to 60 days to allow for filing a Patent Application (if applicable). No publication of single center data should be done prior of publication if multi-center data.
Results Point of Contact
| Name/Title | Therapeutic Area Head |
|---|---|
| Organization | BAYER |
| Phone | |
| clinical-trials-contact@bayerhealthcare.com |
- 11726
- 2008-000107-28